Overall objectives are to discover small molecule drug leads against a targeted group of diseases critical to developing nations and to the United States, by using ecological insights to guide the investigation of novel natural products from biodiverse coral reef organisms and marine microbes of Fiji. The project also helps build local institutions and attitudes to conserve marine biodiversity of the South Pacific, and undertakes this goal in ways that provide positive economic incentives for the owners of these marine environments. These efforts will found the South Pacific Center for Biodiversity Conservation and Drug Discovery at the University of the South Pacific (USP). This center will serve the 12 island nations that own USP (Cook Islands, Fiji, Kiribati, Marshall Islands, Nauru, Niue, Samoa, Solomon Islands, Tokelau, Tonga, Tuvalu and Vanuatu), and be an independent and self-sustaining unit by the end of the ICBG grant. Specific aims are: To collect, extract, and bioassay 500 samples from marine actinomycetes and 500 samples from coral reef plants and invertebrates each year. To use ecological approaches to induce a greater diversity and potency of natural products from marine organisms for exploration as drug leads. To perform bioassay-guided isolation of active constituents and determine the structure of 25 new bioactive molecules per year. To test these novel natural products against cancer, malaria, HIV-AIDS, tuberculosis, and other infectious disease-causing organisms including drug-resistant Staphylococcus aureus, Enterococcus faecium, and Candida albicans. To promote scientifically-informed coral reef conservation, management, biological monitoring, and alternative income generation that is biodiversity-based and ecologically sustainable. To transfer appropriate technology to Fiji and the proposed South Pacific Center for Biodiversity Conservation and Drug Discovery. [unreadable] [unreadable]